1) Cerebral metabolism was studied in relation to age and drug responses in unanesthetized rats. Regional cerebral glucose utilization (rCMRglc) as measured with 14C-2-deoxy-D-glucose, increased during development in Fischer-344 rats, but remained constant during senescence. 2) Cerebral metabolic rates for 02 and glucose did not decline significantly between 3 and 24 months of age. 3) In adult rats, central muscarinic stimulation with oxotremorine increased rCMRglc in areas involved in motor and cognitive function. Blockade of acetylcholine degradation with physostigmine increased rCMRglc in central optic pathways and the nucleus of the trigeminal nerve. 4) An age effect in the rCMRglc response to oxotremorine was observed during the second year of life in rats. 5) GABA agonists generally decreased rCMRglc, but produced a relative increase in the dentato-rubro-thalamic pathway. 6) There is a clear relation between loss of retinal photoreceptors during aging of the albino rat, and the decline in glucose utilization. 7) Incorporation of 14C-palmitate in the rat brain can be employed to quantitatively examine regional function.